Submit Manuscript  

Article Details


Exploring Proteomic Drug Targets, Therapeutic Strategies and Protein- Protein Interactions in Cancer: Mechanistic View

[ Vol. 18 , Issue. ]

Author(s):

Khalid Bashir Dar, Aashiq Hussain Bhat, Shajrul Amin, Syed Anjum, Bilal Ahmad Reshi, Mohammad Afzal Zargar, Akbar Masood and Showkat Ahmad Ganie*Pages 1-19 (19)

Abstract:


Protein-protein interactions (PPIs) drive major signalling cascades and play critical role in cell proliferation, apoptosis, angiogenesis and trafficking. Deregulated PPIs are implicated in multiple malignancies and represent the critical targets for treating cancer. Herein, we discuss the key protein- protein interacting domains implicated in cancer notably PDZ, SH2, SH3, LIM, PTB, SAM and PH. These domains are present in numerous enzymes/kinases, growth factors, transcription factors, adaptor proteins, receptors and scaffolding proteins and thus represent essential sites for targeting cancer. This review explores the candidature of various proteins involved in cellular trafficking (small GTPases, molecular motors, matrix-degrading enzymes, integrin), transcription (p53, cMyc), signalling (membrane receptor proteins), angiogenesis (VEGFs) and apoptosis (BCL-2family), which could possibly serve as targets for developing effective anti-cancer regimen. Interactions between Ras/Raf; X-linked inhibitor of apoptosis protein (XIAP)/second mitochondria-derived activator of caspases (Smac/DIABLO); Frizzled (FRZ)/Dishevelled (DVL) protein; beta-catenin/T cell factor (TCF) have also been studied as prospective anticancer targets. Efficacy of diverse molecules/ drugs targeting such PPIs although evaluated in various animal models/cell lines, there is an essential need for human-based clinical trials. Therapeutic strategies like the use of biologicals, high throughput screening (HTS) and fragment-based technology could play an imperative role in designing cancer therapeutics. Moreover, bioinformatic/computational strategies based on genome sequence, protein sequence/structure and domain data could serve as competent tools for predicting PPIs. Exploring hot spots in proteomic networks represents another approach for developing targetspecific therapeutics. Overall, this review lays emphasis on a productive amalgamation of proteomics, genomics, biochemistry, and molecular dynamics for successful treatment of cancer.

Keywords:

Computational methods, drug targets, proteomics, small molecule inhibitor.

Affiliation:

Department of Clinical Biochemistry, Faculty of Biological Sciences, University of Kashmir, Srinagar, Department of Clinical Biochemistry, Faculty of Biological Sciences, University of Kashmir, Srinagar, Department of Biochemistry, Faculty of Biological Sciences, University of Kashmir, Srinagar, Amity Institute of Biotechnology, Amity University, Rajasthan, Department of Biotechnology, Faculty of Biological Sciences, University of Kashmir, Srinagar, Department of Clinical Biochemistry, Faculty of Biological Sciences, University of Kashmir, Srinagar, Department of Clinical Biochemistry, Faculty of Biological Sciences, University of Kashmir, Srinagar, Department of Clinical Biochemistry, Faculty of Biological Sciences, University of Kashmir, Srinagar



Read Full-Text article